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Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder. Affected persons suffer from recurrent infections of upper and lower airways because of highly reduced numbers of multiple motile respiratory cilia. Here we report recessive loss-of-function and missense mutations in MCIDAS -encoding Multicilin, which was shown to promote the early steps of multiciliated cell differentiation in Xenopus . MCIDAS mutant respiratory epithelial cells carry only one or two cilia per cell, which lack ciliary motility-related proteins (DNAH5; CCDC39) as seen in primary ciliary dyskinesia. Consistent with this finding, FOXJ1-regulating axonemal motor protein expression is absent in respiratory cells of MCIDAS mutant individuals. CCNO , when mutated known to cause RGMC, is also absent in MCIDAS mutant respiratory cells, consistent with its downstream activity. Thus, our findings identify Multicilin as a key regulator of CCNO/FOXJ1 for human multiciliated cell differentiation, and highlight the 5q11 region containing CCNO and MCIDAS as a locus underlying RGMC. Reduced generation of multiple motile cilia (RGMC) is a rare mucociliary clearance disorder, characterized by chronic airway disease. Here, the authors identify mutations in the Multicilin gene, MCIDAS , and suggest that these mutations cause RGMC through disruption of multiciliated cell differentiation.

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

Fiberoptic flexible laryngoscopy (FFL) is the diagnostic procedure of choice in patients with laryngomalacia. Two techniques can be applied, either when the infant is awake or using anesthesia/sedation. The choice of technique may effect the diagnosis. To compare the two techniques for diagnosing laryngomalacia. A total of 42 infants who underwent awake fiberoptic laryngoscopy for congenital stridor, in whom either laryngomalacia was diagnosed or no cause for stridor was found, underwent a repeat laryngoscopy using anesthesia/sedation. The 84 video recordings of the supraglottic portions were copied onto a videotape along with 25 recordings of normal upper airways without stridor and 31 duplicate cases with stridor. A total of 140 recordings was mixed at random on a videotape. Sound was not included. Three investigators (Y.S., J.B.A., and A.D.) independently scored each recording using a laryngomalacia scoring system (scoring range, 0 to 8). A threshold score of 2 was the optimal cutoff point for discriminating laryngomalacia from normal condition. The awake technique (WT) missed three cases of laryngomalacia and overdiagnosed one healthy control subject. The anesthesia technique was superior with a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100% compared with 93%, 92%, 97%, and 79%, respectively, for the WT. The diagnosis of laryngomalacia with FFL is more accurate using anesthesia/sedation. The WT may be appropriate for screening or for patients with mild cases having a characteristic presentation.

Purpose Lung inflammation from exposure to airborne particulate matter (PM) may be responsible for morbidity in asthma, but several studies using environmental monitoring data showed inconsistent results. Thus, the aim of this study was to evaluate the capability of induced sputum (IS) technology in order to biologically monitor PM in the lungs of urban asthmatic children. Methods We collected clinical, demographic, biological and environmental monitoring data on 136 children referred for asthma evaluations. The study participants were divided into two groups according to IS eosinophil counts of <3 % (non-eosinophilic inflammation, n  = 52) and ≥3 % (eosinophilic inflammation, n  = 84). Results The eosinophilic group displays significantly higher levels of fractional exhaled nitric oxide than the non-eosinophilic one (58.8 ± 47.5 vs 28.9 ± 34.2 ppm, p  = 0.007). Particles (0–2.5 and 0–5 µm) comprised a strong risk factor for eosinophilic inflammation in IS (≥3 %). Children with >80 % of particles (0–2.5 µm) out of the total PM accumulated in the airways displayed the highest OR 10.7 (CI 2.052–56.4 p  = 0.005) for an existing eosinophilic inflammation. Heme oxygenase-1 (HO-1) enzyme levels in IS positively correlated with % eosinophils and with particles in IS ranging between 2 and 3 μm. The level of HO-1 enzyme activity and FEV1/FVC in children with <3 % eosinophils, but not ≥3 %, was positively and significantly correlated, showing a protective effect of HO-1. Conclusion Accumulation of PM involves oxidative stress pathways and is a risk factor for developing eosinophilic inflammation in asthmatic children. IS can biologically monitor this process.

Fiberoptic flexible laryngoscopy (FFL) is the diagnostic procedure of choice in patients with laryngomalacia. Two techniques can be applied, either when the infant is awake or using anesthesia/sedation. The choice of technique may effect the diagnosis. To compare the two techniques for diagnosing laryngomalacia. A total of 42 infants who underwent awake fiberoptic laryngoscopy for congenital stridor, in whom either laryngomalacia was diagnosed or no cause for stridor was found, underwent a repeat laryngoscopy using anesthesia/sedation. The 84 video recordings of the supraglottic portions were copied onto a videotape along with 25 recordings of normal upper airways without stridor and 31 duplicate cases with stridor. A total of 140 recordings was mixed at random on a videotape. Sound was not included. Three investigators (Y.S., J.B.A., and A.D.) independently scored each recording using a laryngomalacia scoring system (scoring range, 0 to 8). A threshold score of 2 was the optimal cutoff point for discriminating laryngomalacia from normal condition. The awake technique (WT) missed three cases of laryngomalacia and overdiagnosed one healthy control subject. The anesthesia technique was superior with a sensitivity of 100%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 100% compared with 93%, 92%, 97%, and 79%, respectively, for the WT. The diagnosis of laryngomalacia with FFL is more accurate using anesthesia/sedation. The WT may be appropriate for screening or for patients with mild cases having a characteristic presentation.

Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback. Results: 14 centers participating in the consortium successfully completed the revised version of the questionnaire for 173 patients with various completion rates for various items. While content and internal consistency analysis demonstrated validity, there were methodological deficiencies impacting completion rates and end-user utility. These deficiencies were addressed resulting in a more valid questionnaire. Conclusions: Our experience may be useful for future clinical research in PCD. Based on the feedback collected on the questionnaire through analysis of completion rates, judgmental analysis of the content, and feedback from experts and end users, we suggest a practicable framework for development of similar tools for various future PCD research.

Congenital pulmonary lymphangiectasis (CPL) is a rare cause of respiratory distress in neonates and infants. Soferman et al present three cases in whom congenital pulmonary lymphangiectasis symptoms appeared during infancy after an uneventful neonatal period. After conducting clinical trials and laboratory evaluation of the three infants, it was found out that cytometric analysis of the broncho-alveolar lavage fluid in two cases revealed high eosinophil levels.